4h-1, 3-oxazine-4, 6 (5h)-diones and their preparation



United States Patent 3,394,132 4H-1,3-0XAZINE-4,6(5H)-DIONES AND THEIR PREPARATION James C. Martin and Paul G. Gott, Kingsport, Tenn., as-

signors to Eastman Kodak Company, Rochester, N.Y.,

a corporation of New Jersey No Drawing. Filed Mar. 31, 1966, Ser. No. 538,981 6 Claims. (Cl. 260-244) ABSTRACT OF THE DISCLOSURE 4H-l,3-oxazine-5,6(5H)-diones, prepared by reacting an acyl isocyanate with a substituted ketene, are useful as intermediates in the preparation of N-acylmalonamates which in turn are useful as plasticizers.

This invention relates to certain oxazinediones as novel compositions of matter. It further relates to a method for combining acyl isocyanates with disubstituted ketenes to produce novel oxazinediones. Furthermore, it relates to a method for combining 4H-1,3-oxazine-4,6(5H)-diones with an alcohol to produce N-acylmalonamates.

A review of the literature reveals that the oxazinedione compounds and processes of this invention have not been reported. Although there is no mention in the literature of the 4H-l,3-0xazine-4,6(5H)-diones, sulfonyl azetidinediones have been reported. German Patent No. 1,098,515 describes the addition of sulfonyl isocyanates to ketenes to give the 4-membered ring products--the sulfonyl azetidinediones.

It is an object of this invention to provide certain oxazinediones as new compositions of matter.

Another object is to provide a method for preparing certain oxazinediones by reacting acyl isocyanates with substituted ketenes.

Yet another object is to provide a method for preparing N-acylrnalonamates by combining certain novel oxazinediones with alcohol.

These and other objects are attained by the practice of this invention which, briefly, comprises combining a disubstituted ketene with an acyl isocyanate, usually in an inert solvent, and isolating the solid ox-azinedione product. The resulting oxazinedione product may be combined with an alcohol to give N-acylmalonarnates.

More specifically, the certain oxazinediones are obtained by reacting an acyl isocyanate having the formula R It'd No 0 with a substituted ketene having the formula and providing 4H-l,3-oxazine-4,6(SID-diones having the formula wherein R is selected from the group consisting of aliphatic and cyclo aliphatic having from 1 to 16 carbon atoms and mono-nuclear aryl having from 6 to 10 carice bon atoms; the substituents R and R when taken singly, are selected from the group consisting of alkyl having from 1 to 12 carbon atoms and mononuclear aryl having from 6 to 10 carbon atoms, and the substituents R and R when taken collectively with the carbon atom to which they are attached, represent joined alkylene groups completing a carbocyclic ring of 4 to 10 ring carbon atoms.

The acyl isocyanates that are suitable for use in the present invention are well-known compounds. A convenient synthesis for this class of compounds has been described by Speziale and Smith in J. Org. Chem, 27, 3742 (1962). Some acyl isocy-anates that are suitable for use in the present invention are: chloroacetyl isocyanate, phenyl-acetyl isocyanate, diphenylacetyl isocyanate, benzoyl isocyanate, p-methoxybenzoyl isocyanate, p-chlorobenzoyl isocyanate, trichloromethylacetyl isocyanate, methylbenzoyl isocyanate, m-methylbenzoyl isocyanate, o-rnethylbenzoyl isocyanate, m-nitrobenzoyl isocyanate, aceyl isocyanate, propionyl isocyanate, isobutyryl isocyanate, dodecanoyl, isocyanate, stearoyl isocyanate, etc.

Aliphatic groups Which may be used as the group R in this invention are alkyl and alkyl groups substituted with halogens, phenyls, etc.

Ketenes and their use in chemical reactions are old. Ketenes that are suitable for use in this invention include the disubstituted ketenes, i.e., dialkyl, diaryl and alkylarylketenes. Typical ketenes which may be employed include the following: dimethylketene, diethylketene, methylpropylketene, butylethylketene, isobutylethylketene, dibutylketene, dihexylketene, dioctylketene, pentamethyleneketene, ethylmethylketene, diphenylketene, ditolylketene, ethylphenylketene, methylphenylketene, dibenzylketene, etc. Suitable ketenes are described by Hanford and Sauer in Organic Reactions, vol. III, Roger Adams, editor, John Wiley and Sons, Inc., New York, 1946, pp. 108-140. Dialkylketenes, which are used in this invention, may also be prepared by pyrolyzing anhydrides of dialkylacetic acids to the corresponding dialkylketenes and dialkylacetic acids in accordance with the process disclosed in Hasek et al., U.S. Patent 3,201,474.

In the process for preparing 4H-1,3-oxazine-4,6(5H)- diones by reacting ketenes with acyl isocyan'ates, it is not necessary to use a solvent, but it is frequently advantageous to do so. Suitable solvents include esters, ethers, aliphatic and aromatic hydrocarbons and chlorinated hydrocarbons, nitriles, etc., and also certain dipolar solvents such as nitromethane, nitrobenzene, dimethylformamide, dimethylacetarnide, tetramethylene sulfone, propylene carbonate, dimethylsulfoxide, etc.

The temperature of the subject reaction is generally governed by the nature of the reactants. However, temperatures ranging from 0 to 180 C. may be used.

An equimolar ratio of acyl isocy-anate to ketene is generally used although an excess of either reactant is not detrimental to the reaction.

The 4H-1,3-oxazine-4,6(5H)-diones produced by this invention are useful as intermediates in the preparation of plasticizers. The esters, N acylmalona'mates, obtained from the reaction of alcohols with 4H-1,3-oxazine-4,6(5H)- diones are useful as plasticizers for various reisns, e.g., cellulose acetate butyrate. Example 8 exemplifies the use of the N-acylmalonamates as plasticizers.

The following examples illustrate the best modes con tcmplated for carrying out this invention.

Example 1 To a stirred solution of benzoyl isocyanate (15 g.; 0.11 .mole) in benzene ml.) was added dimethylketene 3 (11.9 g.; 0.17 mole). The reaction was exothermic and the temperature was kept at 2540 C. by means of a cooling bath. The solvent was removed in vacuo and the solid residue was recrystallized from benzene to give 5.5 g. of 5,5 dimethy1-2z-phenyl-4H-1,3'oxazine-4,6(5H)-dione, M.P.133135 C.

Analysfs.-Calcd. for C12H11NO3 C, H, N, 6.5. Found: C, 65.9; H, 5.2; N, 6.3.

The structure of the product in Example 1 was proven by hydrogenation to N-benzyl-2,2-dimethylmalnamic the followm Example 3 The following equation illustrates the reaction that A mixture of benzoyl isocyanate (4 0027 mole) took p diphenylketene (5 g.; 0.026 mole) and benzene (5 ml.) 0 was refluxed for 5 hours. The crystals that formed on cooling were removed by filtration and dried to ive 4.2 o o o 1) g H g. of 2,5,5-tr1phenyl 4H-1,3-oxaz1ne 4,6(5H)-dione, cu-ncNco (cm)2c==0 E FK MP. 161.5163.5 c. (decomp).

N-C The following equation represents the reaction that took place. 1 2t) 0 Examp e 2 To a stirred solution of trichloroacetyl isocyanate (5.7 V a g.; 0.03 mole) in benzene (30 ml.) was added dimethylclHficNco (OBH5)1CCO C5H5C\ C(CEHE), ketene (2.1 g.; 0.03 mole). The exothermic reaction was Nc|) kept at -40 C. by a cooling bath. The solid that 29 0 formed was removed by filtration and dried to give 6.0 g. of 5,5-dimethyl Z-trichloromethyl 4Hl,3-oxazine E I A 4-,6(5H)-dione. Recrystallization from a mixture of ben- Xamp e zone and hexane gave a product melting at 152-155" C. Under the general conditions of Example 2, the iso- Analysis.-Calcd. for C H Cl NO C, 32.5; H, 2.3; 30 cyanates and ketenes listed in the following table give N, 5.4. Found: C, 32.8; H, 2.4; N, 5.2. the indicated products.

Isoeyauntc Kotene Product 0 I! i NOZ-CNCO (C4I'Ig)gC C O NO --C /c o.rr,

ll 0 Ii 5) o-c CiClizCNCO (CsHr7)z CICI'IQC s i7)2 o ll 0 C0115 OC C5115 i! CHIIQQCNCO C=C=O 011E c on; N-(fi CH3 O H o 00 H (ctHmcHcNcO (cnn c czo ctHmCHc C(CHQ);

if (I) OC\ o1 -(':Nco cunomno=o=o o1-- 4; momenta,

NEII/ 0 H /o C The foregoing oxazinediones also maybe reacted with wherein R, R and R respectively are as previously described and R is selected from the group consisting of 7 alkyl or substituted alkyl having from 1 to 16 carbon atoms, and mononuclear aryl having 6 to 10 carbon atoms.

In addition the oxazinediones may also be hydrogenated to provide N-acylmalonamic acid having the formula wherein R, R and R respectively are as previously described.

Suitable alcohols which may be used include methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, octyl alcohol, isooctyl alcohol, decyl alcohol, lauryl alcohol, benzyl alcohol, etc. Phenols and substituted phenols are also suitable.

Thereaction maybe carried out in a solvent. Suitable solvents include ethers, esters, aliphatic and aromatic hydrocarbons and chlorinated hydrocarbons. However an excess of alcohol may be used as thesolvent.

The process for the reaction of'the oxazinedione with alcohol may beoperated withoutaa catalyst. However, it is preferred to use a catalyst and maintain the temperature Within the range from to 200 C. Catalytic agents that may be used are basic materials and include sodium carb0riate, sodium hydroxide, sodium alkoxides, triet hylenediamine, benzyltrimethylammonium hydroxide, etc.

The following examples describe some typical reactions in which the above oxazinediones are converted to N- acylmalonamates ;and; N*acylmalonamic acid: The ester may be obtained by combining the oxazinedione with an alcohol. The acid may be obtained by hydrogenating the oxazinedione.

Example '5 p 1 :..,'A solution of 5,S-dirnethy1-2 phenyl-4H-l,3.-oxazine-4,6 .(5H-)-'dion' e (5 g. 0.023mole) in toluene (200 ml.) was hydrogenated 'ina' magnetically stirred pressure bottleiat 40 p.' 's.i;.and 2 52C: over 5% palladium (2g) on carbon. .The catalyst wasremovedby filtration and washed with ,7; of acetone. All'filtrates and extracts were combined and evaporated in vacuo to give 3.1 g. (60% of crude hl-benzyl-2,2;dimethylmalonamic acid. Recrystallization from toluene gave material melting at 112-114 C. Infrared absorptions (KBr), 3.00, 3.6 "to 4.4, 5.83 to 6.23 and 6.50 1; n.m.r. spectrumv (C H Cl singlet at 1.49, 6H(methyl groups), doublet of 4.46, 2H(methylene group), broad peak at 7.00, 1H (-NH)', singlet at 7.29, 5:H(aromatic.protons), and a singlet at 11.23, 1H ppm.

Analysis.Calcd.. for C H NQ C, 65.1; H, 6.8; N,

' ing equation:"

The reaction that took place is illustrated by the follow- Example 6 A mixture of 5,5-dirnethyl-2-phenyl-4H-1,3-oxazine-4,6

- (5H)-dione (2.17 g.; 0.01 mole), sodium methoxide (0.1 g.) and methanol (15 ml.) heated up spontaneously and the solid went into solution. After standing for 12 hrs. at room temperature, the solvent was removed in vacuo. The viscous residue was treated with 6 ml. of water to effect crystallization. Filtration gave 1.2 g. (48%) of methyl 'N-benzoy1-2,Z-dimethylmalonainate. A sample after recrystallization from carbon tetrachloride melted at 69-71 C. Infrared absorptions (KBr), 3.0, 5.75, 5.90 and 6.0 n.m.rspectrum (CHCl sing1et at 1.56, 6H(gemdimethyl group), singlet at 3.81, 3H('met hoxy group), multiplets at 7.53, 3H and 7.95, 2H (aromatic protons), and broad singlet at 10.15, 1H p.p.m. NH).

Analysis.-Calcd. for C H NO C, 62.6; H, 6.1; N, 56. Found: C, 62.8; H, 6.2; N, 5.3.

The reaction that took place is illustrated by the following equation:

Example 7 Using the general procedure described in Example 6, 5,5-dimethyl-2-phenyl-4H-1,3-oxazine-4,6-(5H)-dione and n-decyl alcohol give decyl N-benzoyl-2,Z-dimethylmalonamate. V I

The following equation represents the reaction that took place.

Example 8 on heated rolls. The resulting resin is quite tough, has

good appearance and isveasy to mold.

Example 9 Under the general conditions described in Example 6, the following 4H-1,3-oxazine-4,6(5H)diones and alcohols F 6.3. Found C, H, 6.9; M, 7.0. react to give the indicated products.

5 f Oiraiinedione- Alcohol Product I I? V 0-0 0H 0 o o H 1 u u u NOz- C C(C-JIQZ cmoHom No I oNnocwil-mlco011mm),

Oxazinedione Alcohol Product if t if? i C1 I-I C /c C4II9OH 0111 12; CNHC clC (34H,

N-(fl) CH; C6H5 0 ll O c u Ii 11 (CSH)2CIIO C(CH 0161 133011 (CgH5) OH-CNHCC(CH );C00 011 -0 II o i 1i i i o1-o /C(CH2CQI'I5)2 Q-OH Cl-Q-CNHC-C(CH CdlshCO-Q Example 10 0 2 1 Under the general conditions of Examples 6, 5,5-di- 0 methyl-2-phenyl-4H-1,3-oxazine-4,6(5H)-dione (2.17 g.; ee C(CHK), 0.01 mole), triethylenediamine (0.05 g.) and methanol (10 ml.) give methyl N-benzoyl-Z,Z-dimethylmalonarnate.

Example 11 wherein R is alkyl or chloroalkyl of 1 to 16 carbon atoms, benzyl, phenyl, chlorophenyl, nitrophenyl, or tolyl; the substituents R and R when taken singly, are alkyl of l to 12 carbon atoms, benzyl, or phenyl and the subsubstituents R and R when taken collectively with the carbon atom to which they are attached, represent joined alkylene groups completing a carbocyclic ring of 4 to 10 ring carbon atoms.

2. A compound as defined in claim 1 having the formula:

3. A compound as defined in claim 1 having the formula:

4. A compound as defined in claim 1 having the formula:

5. A process which comprises mixing'an acyl isocyanate of the formula:

3 RCNCO with a substituted ketene of the formula:

C=C=O a wherein R is alkyl or chloroalkyl of 1 to 16 carbon atoms, benzyl, phenyl, chlorophe'nyl, nitrophenyl, or tolyl; the substituents R and R when taken singly, are alkyl of 1 to 12 carbon atoms, benzyl, or phenyl and the substituents R? and R when taken collectively with the carbon atom to which they are attached, represent joined alkylene groups completing a'carbocyclic ring of 4 to'l0 ring carbon atoms. V

6. A process according to claim 5 in which the 'temperature is in the range of 0 to C.

MOTHER REFERENCES Grafet al.: German application 1,098,515 (12 p. 5) February 1961, 260-239, 2 pages spec.

Gunar et a1.: Izves. Akad. Nauk SSSR Ser.. Khim. 1965, pp. 1076-7.

HENRY R. JILES, Primary Examiner. NATALIE TROUSOF, Assistant Examiner. 

